Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001435850 | SCV001638680 | likely benign | Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 | 2024-01-22 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001356662 | SCV001551892 | benign | not specified | no assertion criteria provided | clinical testing | The IFIH1 p.Leu690Pro variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs189782013) and in control databases in 25 of 242786 chromosomes at a frequency of 0.000103 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the East Asian population in 25 of 17988 chromosomes (freq: 0.00139), but not in the African, Latino, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Other, and South Asian populations. The p.Leu690 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. |